The end of my Omega-3 Part II post presented evidence that high concentrations of DHA in mitochondrial inner membrane (MIM) could accelerate aging by causing more oxidative damage. However, I left with the question of whether dietary consumption of DHA could affect those concentrations. In this post, I am going to present some research discussing effects of the dietary DHA consumption/supplementation, and I am trying to determine how DHA supplementation affects MIM concentrations of long-chain PUFAs and whether benefits of mild/moderate DHA supplementation would out weight potential aging effects.  

NOTE: One point I want to mention before diving in is EPA & DHA have anti-inflammatory (and other beneficial) effects within the body. So, for some people, supplementation can definitely be beneficial. For people with health problems leading to inflammation or inflammatory diets, the supplementation benefits would likely out weigh the effects of MIM oxidation. There is also evidence that DHA supplementation can help people with autoimmune diseases, and possible bi-polar disorder. Also, pregnant women would benefit from DHA supplementation. So, I am not trying to make a broad argument either for or against EPA/DHA supplementation, but rather trying to determine whether is it right for me *and* what type of supplementation I want to recommend to family and friends. I am following a very specific dietary regimen, so what may be in my best interest may not provide the same benefit to others following a more conventional dietary approach.

Docosahexaenoic acid prevents dendritic cell maturation and in vitro and in vivo expression of the IL-12 cytokine family 
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Differential effect of maternal diet supplementation with alpha-Linolenic adcid or n-3 long-chain polyunsaturated fatty acids on glial cell phosphatidylethanolamine and phosphatidylserine fatty acid profile in neonate rat brains.
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Fish oil increases mitochondrial phospholipid unsaturation, upregulating reactive oxygen species and apoptosis in rat colonocytes.
The researchers in this study have an interest in colon cancer rather than aging, but their results on DHA supplementation and mitochondrial cell membranes happens to be relevant from an anti-aging perspective. In order to further understand the protective effects of DHA and fiber consumption had against colon cancer, the researchers speculated that the lipid component of the diets they were observing (corn oil vs fish oil…..linolic acid vs. EPA/DHA), changes the unsaturation in the mitochondrial membrane making them more susceptible to reactive oxygen species (ROS….oxidative damage). Keep in mind this study only focuses on the mitochondria in the colon, BUT they referenced two papers analyzing the mitochondria from heart and liver tissue that resulted in the same dietary effects. (link1, link2)

To test their theory, rats were given diets with three different types of fat: fish oil, corn oil, or a FAAE: fatty acid ethyl ester (to mimic the fatty acid composition of fish oil, but in a purified form). The mitochondria from the cells in the rat’s colonic crypts were analyzed after being fed the specialized diet for 2 weeks.

Both the fish oil and FAEE diets increased the levels of unsaturation (the higher the degree of unsaturation, the greater number of rings, double, ,or triple bonds in a molecule) in the mitochondrial membrane phospholipids, and these rats had higher levels of unsaturation than the corn oil fed rats.

They observed a strong correlation between ROS and the degree of unsaturation, but only in one area: ROS increased as the degree of unsaturation in the membranes increased BUT only significantly for the cardiolipin fraction WHICH IS ONLY IN THE INNER MEMBRANE. There was not a significant association between ROS and other areas of the mitochondrial membrane although the fish oil and FAEE diets did show increased ROS.

Also, the researchres refrence a study that found: “Oxidative damage to the cardiolipin has been shown to result in a depression of mitochondrial function” (ref: Mitochondria and Apoptosis)

The conclusion of this paper, which supports evidence in other research studies, was that dietary consumption of different fats changes the lipid concentrations in colon cell mitochondrial membrane phospholipids. A diet high in DHA/EPA can cause these membranes to have a higher degree of unsaturation (more DHA in the membrane) and, at least in the cardiolipin component of the mitochondrial inner membrane, it can cause higher rates of oxidative damage.

From the perspective of controlling cancer cells in the colon, this can be good, but from an anti-aging perspective this is likely bad. Those with poor diets and/or high colon cancer risks would likely benefit from DHA supplementation based on these findings, but a person practicing calorie restriction with optimum nutrition would likely not need these particular protective effects. This is not to say there are no beneficial effects of DHA for CRONies, but given that the evidence shows dietary consumption of DHA/EPA can change the degree of unsaturation in colon, heart, and liver cells (what I have personally read, there may be additional studies), the inner mitochondrial membrane is likely compromised by increased ROS activity in all cases.

So, now the question becomes not whether dietary consumption or supplementation can affect DHA/EHA in the mitochondrial membrane, but rather weighing the negative effect the oxidation damage vs other beneficial effects. Also, how much DHA/EPA supplementation is needed to produce a significant oxidative effect, and what level is needed for other beneficial effects? If we consume a high amount of ALA, can our bodies convert enough of the ALA to EPA/DHA to obtain benefit without causing an increase in oxidative effects? And does the rate of DHA incorporation into the mitochondria membrane change for mitochondria in different parts of the body?

As usual, once one question is answered a whole pandora’s box of new questions arise. Stay tuned for further probing into this intriguing topic.      
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